Oral cancer‐associated fibroblasts predict poor survival: Systematic review and meta‐analysis

Abstract

Objectives To perform systematic review and meta‐analysis on correlations between cancer‐associated fibroblasts (CAFs) and the risk of death for patients with oral squamous cell carcinoma. Subjects and methods English literature (1966–2018) was systematically analyzed for studies that immunohistochemically assessed CAF density by alpha‐smooth muscle actin and presented 5 year survival rates by Kaplan–Meier plots. Mean age of patients, proportion of male/female patients, and male/female majority (>50% male/female patients) per study were also collected. Significance level for statistical models was p < 0.05. Results Meta‐analysis comprised 11 studies/1,040 patients. Univariate Cox regressions showed that high CAF density was a negative prognostic factor in studies with female and male majority [OR 5.329 (95% CI 3.223–8.811), p < 0.001, and OR 2.208 (95% CI 1.717–2.839), p < 0.001, respectively]. High CAF density with male majority was associated with a more favorable prognosis [OR 0.996 (95% CI 0.979–1.013), p < 0.001]. Multivariate Cox regressions showed that death risk was significantly higher among patients with high CAF density compared to low CAF [OR 2.741 (95% CI 2.220–3.384) p < 0.001]. High mean age and male proportion were significantly protective [OR 0.940 (95% CI 0.925–9.955), p < 0.001, OR 0.125 (95% CI 0.018–0.867), p = 0.035), respectively]. Conclusions CAFs increased death risk, male majority, and higher mean age were protective. A clinically validated cutoff for CAF density could serve as a reliable prognostic tool.

Cancer-Associated Fibroblast Density, Prognostic Characteristics, and Recurrence in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis

“…The existing literature has suggested that CAFs negatively affect prognostic characteristics in HNSCC but has not produced a uniform conclusion, with some studies failing to show an association and others claiming a strong positive association (20)(21)(22)(23)(24)(25). Two recent meta-analyses have shown that high CAF density is associated with worse overall survival in oral SCC (20,43). This paper sought to clarify the relationship between CAFs, recurrence, and clinicopathologic markers of significance in HNSCC, including 13 independent studies for a study population of over 900 patients.…”

Curcumin suppresses the proliferation and tumorigenicity of Cal27 by modulating cancer‐associated fibroblasts of TSCC

“…In the past decades, increasing evidences have shown that fibroblasts in the TME can impact upon tumor cell biological behavior and can be investigated as a potential target for novel cancer therapies (Hanna, Quick, & Libutti, 2009). CAFs are predominant type of cells found in the TME that actively contributes to tumor growth, invasion, and metastasis (Lin et al, 2017;Sobral et al, 2011), and even the higher density of CAFs predicts the poor prognosis in oral squamous cell carcinoma (OSCC) (Graizel et al, 2020). Therefore, drugs modulating the phenotype and functional features of CAFs would be beneficial and efficient to anti-cancer therapy.…”

Effects of IGF-1 on Proliferation, Angiogenesis, Tumor Stem Cell Populations and Activation of AKT and Hedgehog Pathways in Oral Squamous Cell Carcinoma

“…CAFs participate in angiogenesis, migration, invasion, proliferation and the regulation of signaling pathways, which contributes to tumor severity. In OSCC samples, the presence of CAFs is related to a worse prognosis [35,36]. Initially, we investigated whether fibroblast-secreted IGF-1 provokes non-canonical hedgehog (HH) pathway activation.…”